The preparation and use of 2-amino-5-halo-6-alkyl-4-pyrimidinols as antiviral agents is known (U.S. Pat. No. 3,956,302 and Nicols, Weed and Underwood, Antimicrobial Agents, Chemo. Ther. 9 433, 1976). P reparation of 2-amino-5-bromo-6-phenyl-4-pyrimidinol (V, where X.sub.3 is Br and X.sub.1 is phenyl) has been reported (Brown and Stevens, JCS Perkin I, 1023, 1975) but no utility has been described for this material. Snell, Elias and Freeman in GB 1,223,686 (1967) disclose a variety of 5,6-disubstituted 2-amino-4-pyrimidinols, such as 2-dimethylamino-5-bromo-6-methyl -4-pyrimidinol but do not identify antiviral properties. Various 5-unsubstituted 2-amino-6-arylpyrimidinols are known (e.g., Sirakawa, Yakugaku Zasshi 80, 1542. 1960; Kulkarni et al., J. Sci and Ind. Research (India) 19C, 6-8 (1960), CA 54, 22576C; and U.S. Pat. No. 2,776,283. Diuretics and cardioregulatory properties are-described for various 2-amino and 2-substituted amino-5-aminomethyl and 5 -aryl-6-aryl-4-pyrimidinols, U.S. Pat. No. 2,704,285, U.S. Pat. No. 2,723,977 and U.S. Pat. No. 2,776,283. Again no antiviral properties were noted.
Although 2-amino-5-bromo-6-methyl-4-pyrimidinol (U.S. Pat. No. 3,956,302) exhibits useful antiviral and interferon inducing properties, we have found that its therapeutic application is limited to moderate doses since the material will crystallize in the urine and kidney of animals receiving high therapeutic dose.
The novel 2-amino-6-aryl-5-substituted pyrimidinols of this invention exhibit antiviral activity, an improved therapeutic ratio and fewer side effects and are useful in preventing and treating viral infections. The antiviral activity of many of the compounds of this invention is associated with increased production of interferon. Other compounds of this invention exhibit antiviral activity but do not induce interferon production.